Evaluation of Different Oral Formulations of Clindamycin Extended Release in Dogs.

The purpose of this study was to evaluate the pharmacokinetics of extended-release formulations (ERFs) of clindamycin with polymeric-based matrices. In a crossover study, 21 healthy adult dogs were randomly assigned (in groups of 7) to receive a single oral dose (20 mg/kg) of clindamycin without excipients (control) or an extended-release formulation containing clindamycin+Hydroxypropyl methylcellulose (HPMC)+poloxamer at a ratio of 1 : 0.04 : 0.5 (ERF1) or containing clindamycin+HPMC+acrylic acid polymer (AAP) at the same proportions (ERF2). Serum clindamycin concentrations were determined for pharmacokinetic analysis prior to and at several time intervals after each treatment. Following the oral administration in study dogs, each ERF resulted in therapeutic serum clindamycin concentrations for 60 h, whereas the control treatment resulted in therapeutic serum clindamycin concentrations for only 12 h. All pharmacokinetic parameters for ERF1 and ERF2 were significantly different from those of the control treatment. These results indicate that both ERFs composed of a polymeric matrix containing clindamycin, HPMC, and AAP or poloxamer demonstrated an adequate pharmacokinetic-pharmacodynamic relationship for a time-dependent drug and provided a longer release period than clindamycin alone following oral administration in dogs. Given that the minimum effective serum concentration of clindamycin is 0.3 µg/mL, a dose interval of 60 h could be achieved for each tested ERF. This minimum inhibitory concentration has the potential to be effective against several susceptible bacteria involved in infections in dogs. The treatment of dogs with either ERF may provide several benefits over treatment with clindamycin alone.

Contrasting energy allocation strategies of two sympatric Merluccius species in an upwelling system.

This study investigated the somatic growth and energy allocation strategy of two sympatric hake species (Merluccius polli and Merluccius senegalensis), coexisting under the strong influence of the Mauritanian upwelling. The results revealed that ontogeny, bathymetry, geography and reproduction shaped the differences found between the condition dynamics of the two species. Aside from species-specific differences, individuals were observed in better condition in the northernmost area (more influenced by the permanent upwelling) and in the deepest waters, probably the most favourable habitat for Merluccius spp. Both species also displayed contrasting trade-offs in energy allocation probably due to the dissimilarity of their habitats, which favours the existence of divergent adaptive strategies in response to different ontogenic requirements. It was hypothesized that M. polli invests in mass and energy reserves while sacrificing growth, as larger sizes may not provide an ecological advantage in a deeper and more stable environment. Moreover, M. senegalensis capitalizes on a steady growth without major disruptions, enabling earlier spawning at the expense of a lower somatic mass, which is fitting to a less stable shallower environment. This study sheds new light on differences in the biological traits and life strategies of Merluccius spp., which permit their overlap in a complex upwelling system and may contribute to the long-lasting scientific-based management of these species.

Developmental dysplasia of the hip in neonates: evolution of acetabular dysplasia after hip stabilization by brief Pavlik harness treatment.

BACKGROUND: The recommended treatment duration in neonates with developmental dysplasia of the hip (DDH) varies depending on whether prolonged Pavlik harness therapy is believed to favourably affect the course of the acetabular dysplasia. According to one theory, several months of additional Pavlik harness therapy after achieving hip reduction contributes to correct the acetabular dysplasia. Another theory holds that hip dislocation induces the acetabular dysplasia, which corrects spontaneously once the femoral head is properly seated in the acetabulum. Here, we evaluated this second theory by studying outcomes after early brief Pavlik harness therapy. HYPOTHESIS: Acetabular dysplasia associated with neonatal hip instability undergoes self-correction provided stable hip reduction is achieved very early after birth. Therefore, the duration of Pavlik harness therapy can be substantially shortened. MATERIALS AND METHODS: We defined hip instability as either reducible hip dislocation or a very easily dislocatable hip with a soft clunk precluding determination of spontaneous hip position as dislocated or reduced. Static and dynamic ultrasound scans were obtained. Patients with ultrasonographic instability (pubo-femoral distance>5mm with less than 50% of coverage) underwent a second physical examination and received treatment. We re-evaluated 42 abnormal hips in 30 patients after a mean follow-up of 6.7 years (range, 5-14 years). Mean age at treatment initiation was 5 days (range, 1-15 days) and mean treatment duration was 34 days (range, 15-75 days). RESULTS: Mean acetabular angle was 20° (range, 12°-30°) and mean Wiberg's lateral centre-edge angle was 30° (range, 22°-35°). Blunting of the lateral angle of the bony roof was noted in 8 hips at last follow-up. In 1 patient whose hip was stable clinically but unstable by ultrasonography at 21 days of age, recurrent dislocation occurred at 5 months of age. The Severin class was 1a in all patients. DISCUSSION: Despite continuing controversy about whether hip dislocation induces dysplasia or vice versa, the need for early treatment is universally recognised. The optimal treatment duration, however, remains debated. Proponents of the familial determinism of DDH consider that acetabular shaping is genetically programmed when the femoral head is centred in the acetabular socket. Others advocate routine prolongation of Pavlik harness therapy for 2 months or longer, based on the opinion that this strategy decreases the dislocation recurrence rate and that mechanical hip unloading may promote correction of the dysplasia. Mean treatment duration in our population was 34 days and our sole objective was to treat the instability. The hip was reduced and held in its proper position long enough to allow sufficient capsule and ligament tightening to stabilise the hip. Under these conditions, the acetabular dysplasia underwent self-correction that was not related to treatment duration. CONCLUSION: Very early Pavlik harness therapy to ensure rapid hip reduction and stabilisation optimises the potential of the acetabulum for spontaneous remodelling. LEVEL OF EVIDENCE: Level IV, retrospective study.

Characterization of the inflammatory response in the uteri of cows infected naturally by Neospora caninum.

Bovine neosporosis manifests during gestation, when the fetus may be vulnerable to pathogens. Experimental studies of Neospora caninum-infected cattle have been performed, but little is known about the in-utero inflammatory response. The aim of this study was to characterize the inflammatory response in the uteri of pregnant and non-pregnant cows infected naturally with N. caninum. Four groups of seven animals were studied. Two groups consisted of N. caninum-seropositive pregnant and non-pregnant cows and the other two groups contained N. caninum-seronegative pregnant and non-pregnant cows. Uterine and placental samples were subjected to immunohistochemistry using antibodies specific for N. caninum, CD4, CD8, CD14 and CD21. The non-pregnant seropositive and seronegative groups did not show a difference (P >0.05) in the types of cells present. There were more lymphocytes in the uteri of the seropositive pregnant animals (P <0.05) than in the seronegative pregnant animals, but this was not considered to be consistent with an inflammatory process. N. caninum cysts were detected in eight seropositive cows; five were non-pregnant and three were pregnant. CD4(+) T cells were distributed in the endometrium and myometrium of the non-pregnant cows and were sparse in the placentomes of pregnant cows. CD8(+) T cells were distributed in a similar manner, but were present in smaller number. There were no cells expressing CD14 or CD21. The results of the study suggest that there is no consistent uterine inflammatory response against N. caninum in naturally infected animals.

Paralytic congenital talipes equinovarus of unknown origin: A new entity. Multicenter study of 42 cases.

BACKGROUND: Paralysis of the lateral and/or anterior leg muscles can lead to relapse of treated talipes equinovarus. HYPOTHESIS: The muscle function impairment is due to isolated permanent paralysis, and early palliative tendon transfer may prevent recurrence of the deformity. MATERIAL AND METHODS: Forty-two cases of congenital talipes equinovarus that recurred after conservative therapy were reviewed after a mean follow-up of 10 years. In 39 cases, second-line surgery was performed (posteromedial release, n=33; and muscle transfer, n=26). Outcomes were evaluated clinically. RESULTS: Separating the cases into two groups, based on whether muscle transfer was performed, showed a statistically significant difference: muscle transfer intended to restore eversion and/or dorsal flexion of the foot was associated with significantly better functional outcomes. DISCUSSION: In addition to providing etiological insights, the identification of paralysis in patients with talipes equinovarus can influence treatment decisions, depending on the nature of the muscle deficiencies, with the goal of preventing recurrences. Early muscle transfer to restore eversion and/or dorsal flexion of the foot may provide the best functional outcomes by minimizing the need for soft-tissue release. LEVEL OF EVIDENCE: IV, retrospective multicentre study.

Early correction of paediatric malunited distal metaphyseal radius fractures using percutaneous callus osteoclasis ("Calloclasis").

INTRODUCTION: Closed reduction of secondary displacements of distal metaphyseal radius fractures is an easy procedure only when performed within the first ten to fifteen days post-trauma, prior to the occurrence of malunion. When a hard bony callus prevents proper reduction, an open osteotomy is generally advocated. HYPOTHESIS: We suggest the use of a less invasive technique which aims at correcting early malunion when closed reduction is made impossible: the percutaneous callus osteoclasis. MATERIALS AND METHODS: Callus osteoclasis consists in a series of multiple bone-drilling in a postage stamp pattern performed under image intensifier using a large diameter pin, at a distance from the growth plate. Once the bone has been weakened, reduction is obtained by using the pin as an intrafocal lever. The pin is then pushed through the opposite cortex to ensure postero-lateral stabilization. RESULTS: Twenty-one patients were managed using this technique and reported good results with no complications. DISCUSSION: This technique offers a low aggressive management of malunions and may be performed within two to six weeks after trauma. LEVEL OF EVIDENCE: Level IV. Multicenter retrospective study.

Posteromedial elastic stable intra-medullary nailing (ESIN) in volarly displaced metaphyso-diaphyseal distal radius fractures in child.

INTRODUCTION: The distal metaphyso-diaphyseal fractures of the radius with volar angulation are generally considered unstable. Too distal to be treated with classic elastic stable intramedullary nailing (ESIN) via a laterodistal approach and too proximal to be stabilized with simple conservative treatment, they are sometimes treated by plating. PATIENTS AND METHODS: To avoid the disadvantages of the open exposure necessary for this latter fixation and to prevent volar angulation while respecting the curvature of the radius, radial elastic nailing with posteromedial distal entry was used in 16 patients. These patients were reviewed with an average follow-up of 4.5 months. RESULTS: Six patients presented a mean volar angulation of 7°, eight a mean posterior angulation of 5.5°, and two were aligned at 0°. On the AP view, seven patients presented a mean residual varus of 6.5°, four a mean residual valgus of 5°, and five were at 0°. The pronating curvature of the radius and the radioulnar index remained intact in all cases. One case of extensor digitorum tenosynovitis was observed and disappeared after wire removal. DISCUSSION: For the unstable fractures of the distal third of the radius, certain authors propose systematic classic ESIN, but the lateral point of entry inevitably entails a varus misalignment, which is no longer the case if the entry is medial.

Can Blount's disease heal spontaneously?

INTRODUCTION: In stage 1 of all currently accepted classifications for infantile tibia vara, the diagnosis is difficult between physiological bowing and true Blount's disease. There is no evidence of prognosis criteria for surgical treatment at this stage. PATIENT AND METHODS: We retrospectively studied a series of 26 patients born in the Indian Ocean area, presenting at stage 1 of the disease, in order to determine whether any of them were likely to heal without treatment. RESULTS: It was found that children seen at stage 1 of infantile tibia vara have a one-in-three chance of healing spontaneously. DISCUSSION: An alternative classification in three stages could then provide more suitable therapeutic indications: stage 0: possible Blount's disease (patient older than 2.5 years); stage 1: certain Blount's disease, active physis (+) (progressive varus, age >3 years, typical image with no epiphysiodesis bridging); stage 2: certain Blount's disease, inactive physis (-) (superomedial tibial bony bridge). LEVEL OF EVIDENCE: Level IV. Retrospective study.

Legg-Calvé-Perthes disease treatment by augmentation acetabuloplasty.

INTRODUCTION: Classical surgical treatments for Legg-Calvé-Perthes (LCP) disease are pelvic or femoral osteotomies, which are not without complications and inconvenience for the patient.An effective, relatively undamaging surgical alternative would improve this disease treatment. HYPOTHESIS: Augmentation acetabuloplasty using shelf acetabuloplasty is a recognized treatment for LCP disease, but its results have never been assessed in view of Herring's lateral pillar classification, the current reference in determining the prognosis of this disease. Assessment of its efficacy based on this system is therefore needed. MATERIAL AND METHODS: Over 15 years, 21 patients underwent shelf acetabuloplasty. Included in the study were children with a progressively subluxating femoral head and classified minimum grade B in the lateral pillar classification. The last follow-up had to be at least 12 months after surgery and include a clinical examination as well as an AP pelvic X-ray. RESULTS: The mean follow-up was 4 years and 3 months. Only two complications occurred, one of which required surgical revision. Shelf acetabuloplasty was considered effective (contained and Stulberg 1 or 2) in 13 cases and ineffective (lysed or Stulberg 3, 4, or 5) in eight cases. DISCUSSION: The lateral pillar classification demonstrated its high value in LCP disease in correlation with symptom onset. This series shows that at the medium term, shelf acetabuloplasty is as effective as pelvic or femoral osteotomies for children of any age and any level of disease severity, with fewer complications and less inconvenience for the patient. LEVEL OF EVIDENCE: : Level IV. Therapeutic retrospective study.

Green's surgical procedure in Sprengel's deformity: cosmetic and functional results.

INTRODUCTION: Multiple surgical options are available in the treatment of severe Sprengel's deformities and vary according to the selected muscle disinsertion site. We report here the functional and cosmetic results of the Green's operative technique. MATERIAL AND METHODS: We retrospectively reviewed cases of congenital elevation of the scapula operated on, between 1999 and 2007, at Saint-Denis Regional Hospital Center. Clinical and radiographic examinations along with parents questioning were performed. RESULTS: This study included eight children with a mean follow-up of 4.5 years. Improvement occurred in all cases: the appearance was improved by one grade in three children and two grades in three other children, according to the Rigault's classification system. Cosmetically, all families were satisfied with the final result of the treatment. A case of complete brachial plexus palsy (BPP) that resolved spontaneously within 7 months was observed. DISCUSSION: Sprengel's deformity is an unusual skeletal abnormality. The Green's operative technique allows both lowering and rotation of the scapula. Muscle attachment is distally, rather than proximally, modified which provides a better biomechanical effect: muscles are reattached higher than the acromiothoracic junction's rotation center. The Green's scapuloplasty has been rarely reported in literature, whereas the Woodward procedure remains the reference standard. However, both techniques report similar results. Our choice was based on a better impression in terms of operative approach and improved muscle levers' distance adjustment to the fulcrum. Finally, resection of the superomedial portion of the scapula which is fixed to the rib cage into a pocket of the latissimus dorsi seems to provide a more efficient correction. LEVEL OF EVIDENCE: Level IV, retrospective therapeutic study.

[Early short-term treatment of neonatal hip instability with the Pavlik harness]. / Traitement précoce et court des instabilités néonatales de hanche par harnais de Pavlik.

PURPOSE OF THE STUDY: The purpose of this work was to study early short-term treatment of reducible dislocated or very unstable dislocated hips using the Pavlik harness. This approach is based on the theory of that dislocation favors dysplasia and that spontaneous correction occurs if the hip is reduced and stable. Very easily dislocated hips have been qualified as "major instability" if voluntary dislocation was easily achieved. In this case, it is very difficult to predict whether postnatal capsuloligamentary retraction will occur in the reduced or dislocated position. MATERIAL AND METHODS: We retained for study 34 patients with 44 pathological hips; 15 hips presented reducible dislocation and 29 major instability. Treatment began early at 3.4 days of life on average and lasted 27.9 days. RESULTS: Outcome was very good for 39 hips with stabilization and spontaneous correction of the acetabular dysplasia, good in four with late correction of the dysplasia, and a failure in one. There were no major complications, none of the patients presented post-reduction osteochondritis. DISCUSSION: Two different entities can be distinguished: dislocation producing dysplasia which is symptomatic neonatally and would imply pathogenic in utero events, and primary dysplasia which can be asymptomatic at birth and for which correction is not spontaneous. If the hip is symptomatic at birth, treatment should begin immediately and be continued to confirmation that the reduced hip is stable, i.e. about three to five weeks on average. Simple dysplasia of dislocatable hips should be excluded from this strategy because of their favorable spontaneous course. Likewise for irreducible dislocated hips because of the higher risk of complications. Under these conditions, this therapeutic strategy is effective for the reduction, stability, and correction of dysplasia achieved in 97.7% of cases without increasing the rate of complications.

[Bed rest and skin traction for Perthes' disease: review of the literature]. / La traction au lit dans le traitement de la maladie de Legg-Perthes-Calvé: revue de la littérature.

Long-term bed rest with skin traction, which isolates children with Perthes' disease from their social and educative environment, could be considered as incompatible with the ethics of modern therapeutics. Adaptation for home care has been proposed, but remains burdensome. We searched the literature in order to ascertain the real advantages and disadvantages of bed rest with skin traction and to evaluate the statistical value of published results. Considering that poor outcome is the natural course of the disease in 10-20% of patients, and that the number of patients in this group is further divided according to age and treatment, the number of patients in each treatment arm is rarely sufficient to validate any given treatment. For hips with limited abduction, traction does not appear to be warranted. Conversely, traction could be useful if the aim is to modify the natural course of the disease in precise situations, for example for Herring group B and or B/C patients with bone age above 6 years with a stiff hip. In this case, skin traction should not last more than two weeks and, to be considered useful, should achieve 30 degrees abduction documented on the ap view.

[Immediate weight bearing after treatment of stable epiphysiolysis]. / La mise en charge postopératoire précoce après traitement par vissage des épiphysiolyses stables.

PURPOSE OF THE STUDY: The purpose of this study was to ascertain whether immediate weight bearing after surgery for chronic or stable epiphysiolysis treated with a single percutaneous screw increases the risk of greater displacement. MATERIAL AND METHODS: Epiphysiolysis procedures (n=30) performed in 25 patients were reviewed retrospectively. One percutaneous screw was inserted under fluoroscopic control in all cases. For ten patients (from 2002), weight bearing was allowed immediately after surgery. The Southwick grading system was applied to classify each epiphysiolysis into one of three stages according to the cervicoepiphyseal angle measured on the lateral radiograph. Clinical and radiographic controls were obtained in all children at 1, 3, 6, and 12 months. Outcome was assessed using the Heyman and Herndon criteria. RESULTS: The study population included 17 boys and 8 girls (mean age 12 years 18 months). The left side was involved in 12, the right in 8 and both in 5. Weight bearing was allowed immediately after surgery in 10 patients with a stable epiphysiolysis (4 stage I, 5 stage II, 2 stage III). Time to weight bearing was 3 months on average for the others. Mean follow-up was 4 years (range 1-8 years). Clinically, none of the ten patients presented pain or limping at last follow-up. Abduction was limiting in 9 and internal rotation in 19. There was no increase in the displacement for patients with immediate weight bearing. DISCUSSION: Most teams advise against weight bearing for 6 weeks to 3 months. We were unable to find any pathophysiological reason for this attitude. It would be more logical to wait until complete fusion of the subcapital growth cartilage before authorizing weight bearing. This raises the question of the effect of this practice on postoperative displacement For stable epiphysiolysis, there is no evidence that not allowing weight bearing had an effect on the evolution if the screw is correctly positioned and at least 4 or 5 spires are engaged within the epiphysis.

Liver fibrosis assessment with semiquantitative indexes and image analysis quantification in sustained-responder and non-responder interferon-treated patients with chronic hepatitis C.

BACKGROUND/AIMS: The effect of interferon on the reduction of liver fibrosis is controversial. We aimed to compare semiquantitative methods with a quantitative digital image analysis system to assess liver fibrosis in biopsies from patients with chronic hepatitis and different responses to interferon. METHODS: We studied 98 liver biopsies with chronic hepatitis C before and after recombinant interferon alfa-2 treatment, using conventional histological assessment, grading of histological activity, scoring/staging of fibrosis (Knodell and Scheuer), and quantification of fibrosis with image analysis (FibroQuant). RESULTS: Sustained-responders to interferon showed a significant reduction in histological lesions and in their Knodell and Scheuer activity indexes. The semiquantitative systems showed no reduction in fibrosis. The FibroQuant application showed a significant reduction in porto-periportal and septal areas among sustained-responders (P < 0.001) and non-responders (P < 0.05), and in porto-periportal and septal fibrosis areas only in sustained-responders (P < 0.001), whereas the percentage of fibrosis increased in non-responders (P < 0.001). CONCLUSIONS: The Scheuer system is useful for the daily evaluation of fibrosis, but the FibroQuant application provides more objective data on the anti-fibrogenic effects of interferon, which include a reduction in the porto-periportal area in sustained-responders and non-responders, accompanied by a reduction in the area of fibrosis only when the viral replication has ceased.

[Scarf osteotomy of hallux valgus in children and adolescents]. / Traitement de l'hallux valgus de l'enfant et de l'adolescent par ostéotomie scarf.

PURPOSE OF THE STUDY: The aim of this study was to analyze the results of surgical treatment of hallux valgus using scarf osteotomy in children and adolescents. MATERIAL AND METHOD: Twelve children and adolescents (19 feet) operated on with scarf osteotomy were reviewed retrospectively with a mean follow-up of 15 months. Clinical and radiographic results were assessed. RESULTS: We obtained 10 good results (asymptomatic cases), 9 poor with residual symptoms such as pain or cosmetic problems. Two populations could be identified considering the metatarsus varus and distal metatarsal angle. Those with metatarsus varus >/= 10 degrees or normal distal metatarsal angle had good results. Those without metatarsus varus had poor results. There was no disturbance of growth. DISCUSSION: Scarf osteotomy can be used in children without risk of hindering growth. Nevertheless, good results can be achieved only in cases of true metatarsus varus and normal distal metatarsal angle. In other cases, a different osteotomy of the first metatarsal would be preferable.

[Recurrent aggressive chondroblastoma: two cases and a review of the literature]. / Récidive de chondroblastome agressif.

Chondroblastoma is a rare benign bone tumor. Treatment currently consists of curettage and bone graft. Prognosis depends basically on a relatively high rate of recurrence, between 5 and 38%, sometimes with local seeding of soft tissues and joint space. Such recurrences require wide resection with arthrodesis or even amputation. A 13-year-old girl with a humeral head chondroblastoma as treated by curettage and iliac bone graft. Six months later, a recurrence occurred with extension into the rotator cuff and the metaphysis. Remission was achieved by extensive surgical resection and hemiarthroplasty. The second case was a 14-year-old boy with a chondroblastoma of the right talus. He was treated by curettage and packing with bone substitute. After 2 recurrences with soft tissue and intra-articular extension, we performed a wide resection with reconstruction using a vascularized fibular graft. Many other cases in the literature illustrate such complications. We tried to find factors predictive of recurrence. Recurrence is observed when curettage was incomplete or when tumor cells were disseminated during surgery. Chondroblastoma is a benign bone tumor, but prognosis depends on the rapidity and severity of recurrence. Curettage should be as complete as possible and care should be taken to avoid contaminating the operative field.

Interferon-alpha in patients with chronic hepatitis C and normal transaminase levels.

OBJECTIVE: to assess the response to interferon-alpha therapy in patients with chronic hepatitis C and normal alanine transferase levels. METHODS: 16 patients with normal transaminases (group A) and 36 patients with elevated ALT levels (group B) were treated with interferon-alpha-2b at a dose of 3 MU for 6 months. The biochemical, virological (HCV RNA in serum, liver and peripheral blood mononuclear cells) and histological responses were analyzed. RESULTS: no significant differences were observed between the two groups in age, sex, parenteral or sporadic transmission, hepatic lesion, Knodell index or HCV genotype, except for the higher proportion of women in group A. We found no significant differences between the groups in rates of patients with normal ALT in the follow-up period (6 months post-interferon, group A 44%, group B 17%) or in post-therapy negativization of HCV RNA levels (group A 31%, group B 17%). In 7 patients (44%) in group A, ALT remained normal throughout the study, whereas in the rest of the patients we observed some elevation during or after interferon treatment. Post-therapy mean Knodell index was 6 +/- 3 in group A versus 9 +/- 4 in group B (p < 0.05). CONCLUSIONS: the response to interferon was similar in patients with normal or elevated transaminases.